No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non–small cell lung cancer have been reported.
We conducted a randomized controlled trial to confirm the ...noninferiority of segmentectomy to lobectomy in regard to prognosis (trial No. JCOG0802/WJOG4607L). Patients with invasive peripheral non–small cell lung cancer tumor of a diameter ≤2 cm were randomized to undergo either lobectomy or segmentectomy. The primary end point was overall survival. Here, we have focused on morbidity and mortality. Predictors of surgical morbidity were evaluated by the mode of surgery. Segmentectomy was categorized into simple and complex. Simple segmentectomy was defined as segmental resection of the right or left segment 6, left superior, or lingular segment. Complex segmentectomy was resection of the other segment. This trial is registered with the University Hospital Medical Information Network--Clinical Trial Registry (UMIN000002317).
Between August 10, 2009, and October 21, 2014, 1106 patients (lobectomy n = 554 and segmentectomy n = 552) were enrolled. No mortality was noted. Complications (grade ≥ 2) occurred in 26.2% and 27.4% in the lobectomy and segmentectomy arms (P = .68), respectively. Fistula/pulmonary-lung (air leak) was detected in 21 (3.8%) and 36 (6.5%) patients in the lobectomy and segmentectomy arms (P = .04), respectively. Multivariable analysis revealed that predictors of pulmonary complications, including air leak and empyema (grade ≥ 2) were complex segmentectomy (vs lobectomy) (odds ratio, 2.07; 95% confidence interval, 1.11-3.88; P = .023), and > 20 pack-years of smoking (odds ratio, 2.61; 95% confidence interval, 1.14-5.97; P = .023).
There was no difference in almost any postoperative measure of intraoperative and postoperative complication in segmentectomy and lobectomy patients, except more air leakage was observed in the segmentectomy arm. Segmentectomy will be a standard treatment if the superior pulmonary function and noninferiority in overall survival are confirmed.
The 2 phase III trials, JCOG0802/WJOG4607L and JCOG0804/WJOG4507L, were based on JCOG0201. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Backgrounds
Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is safe and feasible. In contrast, no prospective study evaluating the safety and efficacy of laparoscopy-assisted total ...gastrectomy (LATG) or laparoscopy-assisted proximal gastrectomy (LAPG) has been completed. We conducted a single-arm confirmatory trial to evaluate the safety of LATG/LAPG for clinical stage I (T1N0/T1N1/T2N0) proximal gastric cancer.
Methods
The extent of lymphadenectomy was selected based on the Japanese Gastric Cancer Treatment Guidelines. The mini-laparotomy incision was required to be ≤ 6 cm. The primary endpoint was the proportion of grade 2–4 (CTCAE ver. 4.0) esophagojejunal anastomotic leakage. The planned sample size was 245 considering a threshold of 8% and one-sided alpha of 2.5%.
Results
Between April 2015 and February 2017, 244 eligible patients were enrolled. LATG/LAPG was performed in 195/49. The proportion of conversions was 1.7%. Clinical T1N0/T1N1/T2N0 was 212/9/23. The extents of lymphadenectomy were as follows: D1+: 229; D2: 15. The median operation time was 309 min (IQR 265–353). The median blood loss was 30 ml (IQR 10–86). Grade 2–4 esophagojejunal anastomotic leakage was 2.5% (6/244; 95% CI 0.9–5.3). The overall proportion of in-hospital grade 3–4 adverse events was 29% (71/244). The proportions of intraabdominal abscess and pancreatic fistula were 3.7% and 2.0%, respectively. There were no treatment-related deaths.
Conclusions
This trial confirmed the safety of LATG/LAPG. After the non-inferiority of LADG is confirmed in our phase III trial (JCOG0912), LATG/LAPG is expected to be established as one of the standard treatments for clinical stage I gastric cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional ...fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.
Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided
= .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.
DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
OBJECTIVE:To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer.
BACKGROUNDS:Splenectomy in total gastrectomy is associated with increased operative morbidity and ...mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive.
METHODS:We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%.
RESULTS:Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67–1.16) (<1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025).
CONCLUSIONS:In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.
Background
Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), ...we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer.
Methods
Patients aged 20–75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS).
Results
Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% 95% confidence interval (CI) 54.1–69.6 in Arm A and 60.9% (95% CI 52.7–68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI 0.679–1.236).
Conclusions
For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Endoscopic resection has been limited to intestinal-type gastric cancer (cT1a) with a low risk of lymph node metastasis (T1a ≤2 cm, without ulcers). This single-arm confirmatory trial ...evaluated the efficacy and safety of endoscopic submucosal dissection (ESD) for >2 cm ulcer-negative and ≤3 cm ulcer-positive intestinal-type gastric cancer (cT1a).
Methods
The eligibility criteria included endoscopically diagnosed cT1a, a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size or a ≤3 cm ulcer-positive lesion, cN0M0, and no prior treatment. If ESD resulted in noncurative resection, surgical resection was added. The primary endpoint was the 5-year overall survival (OS) (planned sample size was 470, with a one-sided alpha level of 2.5%). The threshold 5-year OS was 86.1%.
Results
We enrolled 470 early gastric cancer patients median tumor size, 25 (5–130) mm from 29 institutions between June 2007 and October 2010. These patients had 152 ulcer-negative lesions (>2 and ≤3 cm), 111 ulcer-negative lesions (>3 cm), and 207 ulcer-positive lesions (≤3 cm). The success rate for en block resection was 99.1% (466/470). Additional gastrectomy was conducted in 131 patients (28%) who did not fulfill the curative resection criteria. The 5-year OS of all patients was 97.0% (95% confidence interval, 95.0–98.2%), which was higher than the threshold 5-year OS (86.1%). The 317 patients who satisfied the curative resection criteria had no recurrence. There were no ESD-related grade 4 adverse events.
Conclusion
ESD for early gastric cancers that met the expanded criteria for intestinal-type gastric cancer (cT1a) was acceptable and should be the standard treatment instead of gastrectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Backgrounds
No confirmatory randomized controlled trials (RCTs) have evaluated the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG). We performed ...an RCT to confirm that LADG is not inferior to ODG in efficacy.
Methods
We conducted a multi-institutional RCT. Eligibility criteria included histologically proven gastric adenocarcinoma in the middle or lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to ODG or LADG. This study is now in the follow-up stage. The primary endpoint is relapse-free survival (RFS) and the primary analysis is planned in 2018. Here, we compared the surgical outcomes of the two groups. This trial was registered at the UMIN Clinical Trials Registry as UMIN000003319.
Results
Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operative time was longer in LADG than in ODG (median 278 vs. 194 min,
p
< 0.001), while blood loss was smaller (median 38 vs. 115 ml,
p
< 0.001). There was no difference in the overall proportion with in-hospital grade 3–4 surgical complications (3.3 %: LADG, 3.7 %: ODG). The proportion of patients with elevated serum AST/ALT was higher in LADG than in ODG (16.4 vs. 5.3 %,
p
< 0.001). There was no operation-related death in either arm.
Conclusions
This trial confirmed that LADG was as safe as ODG in terms of adverse events and short-term clinical outcomes. LADG may be an alternative procedure in clinical IA/IB gastric cancer if the noninferiority of LADG in terms of RFS is confirmed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of ...preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy.
Methods
We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less.
Results
Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of “cT3/T4 with cN1/N2/N3,” by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%.
Conclusion
Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion “cT3/T4 and cN1/N2/N3” instead.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background Chemotherapy is the standard of care for incurable advanced gastric cancer. Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric ...cancer with a single non-curable factor remains controversial. We aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients. Methods We did an open-label, randomised, phase 3 trial at 44 centres or hospitals in Japan, South Korea, and Singapore. Patients aged 20–75 years with advanced gastric cancer with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2) were randomly assigned (1:1) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution, clinical nodal status, and non-curable factor. Patients, treating physicians, and individuals who assessed outcomes and analysed data were not masked to treatment assignment. Chemotherapy consisted of oral S-1 80 mg/m2 per day on days 1–21 and cisplatin 60 mg/m2 on day 8 of every 5-week cycle. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with UMIN-CTR, number UMIN000001012. Findings Between Feb 4, 2008, and Sept 17, 2013, 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). After the first interim analysis on Sept 14, 2013, the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13·2%, so the study was closed on the basis of futility. Overall survival at 2 years for all randomly assigned patients was 31·7% (95% CI 21·7–42·2) for patients assigned to chemotherapy alone compared with 25·1% (16·2–34·9) for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16·6 months (95% CI 13·7–19·8) for patients assigned to chemotherapy alone and 14·3 months (11·8–16·3) for those assigned to gastrectomy plus chemotherapy (hazard ratio 1·09, 95% CI 0·78–1·52; one-sided p=0·70). The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone: leucopenia (14 patients 18% vs two 3%), anorexia (22 29% vs nine 12%), nausea (11 15% vs four 5%), and hyponatraemia (seven 9% vs four 5%). One treatment-related death occurred in a patient assigned to chemotherapy alone (sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy) and one occurred in a patient assigned to chemotherapy plus gastrectomy (rapid growth of peritoneal metastasis after discharge 12 days after surgery). Interpretation Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours. Funding The Ministry of Health, Labour and Welfare of Japan and the Korean Gastric Cancer Association.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective ...chemoradiotherapy (CRT) based on findings from endoscopic resection (ER).
We performed a prospective study of patients with T1b (SM1–2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed.
Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%–94.7%) and 92.6% in all patients (90% confidence interval, 88.5%–95.2%).
In a prospective study of patients with T1b (SM1–2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.
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